Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction
Authors: Yuejin Yang, Xiangdong Li, Guihao Chen, Ying Xian, Haitao Zhang, Yuan Wu, Yanmin Yang, Jianhua Wu, Chuntong Wang, Shenghu He, Zhong Wang, Yixin Wang, Zhifang Wang, Hui Liu, Xiping Wang, Minzhou Zhang, Jun Zhang, Jia Li, Tao An, Hao Guan, Lin Li, Meixia Shang, Chen Yao, Yaling Han, Boli Zhang, Runlin Gao, Eric D. Peterson, Yuejin Yang, Jianhua Wu, Chuntong Wang, Shenghu He, Zhong Wang, Yixin Wang, Yongquan Jing, Linqiang Liu, Xuxia Zhang, Hanjun Pei, Yuzeng Xue, Guanzhong Zheng, Changyu Wang, Zhongming Zhao, Yanjie Zheng, Baoliang Duan, Gaoxing Zhang, Hui Liu, Zhifang Wang, Zeyuan Fan, Wenzhai Cao, Huanyi Zhang, Xiaoyong Qi, Xiping Wang, Guoqing Wu, Feng Gao, Zidong Bie, Long Yue, Heng Hong, Jun Qian, Bingguang Dai, Weiguang Dou, Liming Yue, Zhongqun Zhan, Man Liu, Xiaohong Gao, Yitian Lian, Yi Zheng, Jiangwu Zhang, Ronghai Man, Peng Dong, Lianling Wu, Junguo Deng, Yong Guo, Minzhou Zhang, Jia Li, Zheying Wang, Peisheng Dai, Guleng Siri, Qiming Xu, Xinyang Li, Keqing Li, Shengli Han, Huaixin Wang, Xia Li, Ping Yang, Haowen Zhang, Yuesen Liu, Bo Xin, Menglang Zhang, Zhiduo Cao, Meng Zhang, Gang Ma, Lei Wang, Jun Song, Weiguo Li, Hongchun Li, Zhenglu Shang, Ouhua Feng, Hongjun Zhang, Hongtao Gao, Rongqi Bao, Fengshun Wang, Linqing Shang, Lei Qin, Jianping Wang, Genshan Ma, Jiayu Cui, Shixi Wang, Fangzhou Cheng, Shujiang Zhang, Xianshi Liu, Chunxi Cha, Min Sun, Wenbao Han, Hang Lu, Haiying Wang, Hongguang Zhu, Wei Wang, Zhili Wang, Yufeng Guo, Haisheng Zhang, Zhong Shao, Xirong Cui, Changlin Lu, Zhan Lv, Jiyin Zhang, Guangkai Cui, Hongwei Zhang, Ying Han, Wenli Liu, Bingfeng Zhou, Hua Ge, Liqun Zhang, Taihong Chen, Bingying Niu, Baoxi Mu, Jiao Zhang, Huaimin Guan, Yuhu Chun, Hua Zhang, Fangjiang Li, Shufang Yin, Xu Wang, Xiao Zou, Junshuai Song, Lang Hong, Mingqi Zheng, Bo Jiang, Shuying Liu, Rui Zhu, Wenbo Liu, Jie Zhang, Bin Wu, Zonggui Wu, Quan Fang, Zuyi Yuan, Chuanyu Gao, Hong Jiang, Xinli Li, Peili Bu, Wei Gao, Hongxu Liu, Ying Xian, Runlin Gao, Boli Zhang, Yaling Han, Junbo Ge, Eric Peterson, Shaoliang Chen, Jielin Pu, Qingshan Zheng, Congxin Huang, Weifeng Shen, Yuan Wu, Chen Yao, Xiaoyan Yan, Meixia Shang, Xiaohan Fan, Huaibing Cheng, Wenlan Chang, Hui Wang, Zhi Li, Wenxuan Zhai, Zhenghui Zhu, Hui Li, Jianpeng Wang, Jin Tao, Bo Xu, Meiying Sun, Fan Wu, Tongqiang Zou, Yue Chang, Peng Yin, Junyan Shen, Yaxing Zhang, Yunfei Huang, Guihao Chen, Xiangdong Li, Yi Xu, Jingang Yang, Haitao Zhang, Chen Jin, Min Wang
Journal: JAMA (2023)

Importance Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], −1.8% [95% CI, −3.2% to −0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, −1.2% [95% CI, −2.5% to −0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, −3.0% [95% CI, −4.6% to −1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, −1.6% [95% CI, −3.1% to −0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (&amp;amp;lt;24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration ClinicalTrials.gov Identifier: NCT03792035